Current Hypertension Reports

, Volume 15, Issue 6, pp 703–716 | Cite as

Association Between Pre-hypertension and Cardiovascular Outcomes: A Systematic Review and Meta-analysis of Prospective Studies

  • Xiaofan Guo
  • Xiaoyu Zhang
  • Liang Guo
  • Zhao Li
  • Liqiang Zheng
  • Shasha Yu
  • Hongmei Yang
  • Xinghu Zhou
  • Xingang Zhang
  • Zhaoqing Sun
  • Jue Li
  • Yingxian SunEmail author
Prevention of Hypertension: Public Health Challenges (NK Hollenberg, Section Editor)



The quantitative associations between prehypertension or its separate blood pressure (BP) ranges and the risk of main cardiovascular diseases (CVDs) have not been reliably documented.


We performed a comprehensive search of PubMed (1966 to June 2012) and the Cochrane Library (1988 to June 2012) without language restrictions. Prospective studies were included if they reported multivariate-adjusted risk ratios (RRs) and corresponding 95 % confidence intervals (CIs) of desirable outcomes, including fatal or non-fatal incident stroke, coronary heart disease, myocardial infarction (MI) or total CVD events, with respect to prehypertension or its separate BP ranges (low range: 120–129/80–84 mmHg; high range: 130–139/85–89 mmHg) at baseline with normal BP (<120/80 mmHg) as reference. Pooled RRs were estimated using a random-effects model or a fixed-effects model.


Twenty-nine articles met our inclusion criteria, with 1,010,858 participants. Both low-range and high-range prehypertension were associated with a greater risk of developing or dying of total CVD (low-range: RR: 1.24; 95 % CI: 1.10 to 1.39; high range: RR: 1.56; 95 % CI: 1.36 to 1.78), stroke (low-range: RR: 1.35; 95 % CI: 1.10 to 1.66; high-range: RR: 1.95; 95 % CI: 1.69 to 2.24) and myocardial infarction (MI) (low range: RR: 1.43; 95 % CI: 1.10 to 1.86; high range: RR: 1.99; 95 % CI: 1.59 to 2.50). The whole range prehypertension had a 1.44-fold (95 % CI: 1.35 to 1.53), 1.73-fold (95 % CI: 1.61 to 1.85), and 1.79-fold (95 % CI: 1.45 to 2.22) risk of total CVD, stroke, and MI, respectively. There was no evidence of publication bias.


Prehypertensive patients have a greater risk of incident stroke, MI and total CVD events. The impact was markedly different between the low and high prehypertension ranges.


Prehypertension Cardiovascular diseases Meta-analysis 


Compliance with Ethics Guidelines

Conflict of Interest

Xiaofan Guo, Xiaoyu Zhang, Liang Guo, Zhao Li, Liqiang Zheng, Shasha Yu, Hongmei Yang, Xinghu Zhou, Xingang Zhang, Zhaoqing Sun, Jue Li, and Yingxian Sun declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


  1. 1.
    World Health Organisation. The global burden of disease: 2004 update. Geneva: World Health Organisation; 2008.Google Scholar
  2. 2.
    Lawes CM, Rodgers A, Bennett DA, Asia Pacific Cohort Studies Collaboration, et al. Blood pressure and cardiovascular diseases in the Asia-Pacific region. J Hypertens. 2003;21:707–16.PubMedCrossRefGoogle Scholar
  3. 3.
    Lawes CM, Vander Hoorn S, Rodgers A, International Society of Hypertension. Global burden of blood-pressure-related disease, 2001. Lancet. 2008;371:1513–8.PubMedCrossRefGoogle Scholar
  4. 4.
    He J, Gu D, Chen J, et al. Premature deaths attributable to blood pressure in China: a prospective cohort study. Lancet. 2009;374(9703):1765–72.PubMedCrossRefGoogle Scholar
  5. 5.
    Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005;365:217–23.PubMedGoogle Scholar
  6. 6.
    Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903–13.PubMedCrossRefGoogle Scholar
  7. 7.
    Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42(6):1206–52.PubMedCrossRefGoogle Scholar
  8. 8.
    Rodgers A, Ezzati M, Vander Hoorn S, Lopez AD, Lin RB, Murray CJ, et al. Distribution of major health risks: findings from the Global Burden of Disease Study. PLoS Med. 2004;1:e27.PubMedCrossRefGoogle Scholar
  9. 9.
    Guo X, Zou L, Zhang X, et al. Prehypertension: a meta-analysis of the epidemiology, risk factors, and predictors of progression. Tex Heart Inst J. 2011;38(6):643–52.PubMedGoogle Scholar
  10. 10.
    Hansen ML, Gunn PW, Kaelber DC. Underdiagnosis of hypertension in children and adolescents. JAMA. 2007;298(8):874–9.PubMedCrossRefGoogle Scholar
  11. 11.
    De Marco M, de Simone G, Roman MJ, et al. Cardiovascular and metabolic predictors of progression of prehypertension into hypertension: the Strong Heart Study. Hypertension. 2009;54(5):974–80.PubMedCrossRefGoogle Scholar
  12. 12.
    Zheng L, Sun Z, Zhang X, et al. Predictors of progression from prehypertension to hypertension among rural Chinese adults: results from Liaoning Province. Eur J Cardiovasc Prev Rehabil. 2010;17(2):217–22.PubMedCrossRefGoogle Scholar
  13. 13.
    Qureshi AI, Suri MF, Kirmani JF, Divani AA, Mohammad Y. Is prehypertension a risk factor for cardiovascular diseases? Stroke. 2005;36(9):1859–63.PubMedCrossRefGoogle Scholar
  14. 14.
    Hsia J, Margolis KL, Eaton CB, et al. Prehypertension and cardiovascular disease risk in the Women’s Health Initiative. Circulation. 2007;115(7):855–60.PubMedCrossRefGoogle Scholar
  15. 15.
    Gu D, Chen J, Wu X, et al. Prehypertension and risk of cardiovascular disease in Chinese adults. J Hypertens. 2009;27(4):721–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epide-miology (MOOSE) group. JAMA. 2000;283:2008–12.PubMedCrossRefGoogle Scholar
  17. 17.
    Guo X, Zhang X, Zheng L, Guo L, Li Z, Yu S, et al. Prehypertension is not associated with all-cause mortality: a systematic review and meta-analysis of prospective studies. PLoS One. 2013;8(4):e61796.Google Scholar
  18. 18.
    Harris RP, Helfand M, Woolf SH, Third US Preventive Services Task Force, et al. Current methods of the US Preventive Services Task Force: a review of the process. Am J Prev Med. 2001;20(3 Suppl):21–35.PubMedCrossRefGoogle Scholar
  19. 19.
    Smith GL, Lichtman JH, Bracken MB, et al. Renal impairment and outcomes in heart failure: systematic review and meta-analysis. J Am Coll Cardiol. 2006;47(10):1987–96.PubMedCrossRefGoogle Scholar
  20. 20.
    Lee M, Saver JL, Chang KH, Liao HW, Chang SC, Ovbiagele B. Impact of microalbuminuria on incident stroke: a meta-analysis. Stroke. 2010;41(11):2625–31.PubMedCrossRefGoogle Scholar
  21. 21.
    Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions. Cochrane Collaboration, 2008.Google Scholar
  22. 22.
    Vasan RS, Larson MG, Leip EP, et al. Impact of high-normal blood pressure on the risk of cardiovascular disease. N Engl J Med. 2001;345(18):1291–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Wu G, Wu Z, Liu J, et al. Impact of high-normal blood pressure on risk of cardiocerebrovascular disease in 11 provinces in China. Zhonghua Yi Xue Za Zhi. 2002;82(16):1083–5.PubMedGoogle Scholar
  24. 24.
    Arima H, Tanizaki Y, Kiyohara Y, et al. Validity of the JNC VI recommendations for the management of hypertension in a general population of Japanese elderly: the Hisayama study. Arch Intern Med. 2003;163(3):361–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Asayama K, Ohkubo T, Kikuya M, et al. Prediction of stroke by self-measurement of blood pressure at home versus casual screening blood pressure measurement in relation to the Joint National Committee 7 classification: the Ohasama study. Stroke. 2004;35(10):2356–61.PubMedCrossRefGoogle Scholar
  26. 26.
    Mainous 3rd AG, Everett CJ, Liszka H, King DE, Egan BM. Prehypertension and mortality in a nationally representative cohort. Am J Cardiol. 2004;94(12):1496–500.PubMedCrossRefGoogle Scholar
  27. 27.
    Liszka HA, Mainous 3rd AG, King DE, Everett CJ, Egan BM. Prehypertension and cardiovascular morbidity. Ann Fam Med. 2005;3(4):294–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Kshirsagar AV, Carpenter M, Bang H, Wyatt SB, Colindres RE. Blood pressure usually considered normal is associated with an elevated risk of cardiovascular disease. Am J Med. 2006;119(2):133–41.PubMedCrossRefGoogle Scholar
  29. 29.
    Terry PD, Abramson JL, Neaton JD, MRFIT Research Group. Blood pressure and risk of death from external causes among men screened for the Multiple Risk Factor Intervention Trial. Am J Epidemiol. 2007;165(3):294–301.PubMedCrossRefGoogle Scholar
  30. 30.
    Wang W, Lee ET, Fabsitz RR, et al. A longitudinal study of hypertension risk factors and their relation to cardiovascular disease: the Strong Heart Study. Hypertension. 2006;47(3):403–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Chien KL, Hsu HC, Sung FC, Su TC, Chen MF, Lee YT. Incidence of hypertension and risk of cardiovascular events among ethnic Chinese: report from a community-based cohort study in Taiwan. J Hypertens. 2007;25(7):1355–61.PubMedCrossRefGoogle Scholar
  32. 32.
    Onat A, Yazici M, Can G, Kaya Z, Bulur S, Hergenç G. Predictive value of prehypertension for metabolic syndrome, diabetes, and coronary heart disease among Turks. Am J Hypertens. 2008;21(8):890–5.PubMedCrossRefGoogle Scholar
  33. 33.
    Gu Q, Burt VL, Paulose-Ram R, Yoon S, Gillum RF. High blood pressure and cardiovascular disease mortality risk among U.S. adults: the third National Health and Nutrition Examination Survey mortality follow-up study. Ann Epidemiol. 2008;18(4):302–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Zhang Y, Galloway JM, Welty TK, et al. Incidence and risk factors for stroke in American Indians: the Strong Heart Study. Circulation. 2008;118(15):1577–84.PubMedCrossRefGoogle Scholar
  35. 35.
    Kokubo Y, Kamide K, Okamura T, et al. Impact of high-normal blood pressure on the risk of cardiovascular disease in a Japanese urban cohort: the Suita study. Hypertension. 2008;52(4):652–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Lee J, Heng D, Ma S, Chew SK, Hughes K, Tai ES. Influence of pre-hypertension on all-cause and cardiovascular mortality: the Singapore Cardiovascular Cohort Study. Int J Cardiol. 2009;135(3):331–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Ikeda A, Iso H, Yamagishi K, Inoue M, Tsugane S. Blood pressure and the risk of stroke, cardiovascular disease, and all-cause mortality among Japanese: the JPHC Study. Am J Hypertens. 2009;22(3):273–80.PubMedCrossRefGoogle Scholar
  38. 38.
    Lorenzo C, Aung K, Stern MP, Haffner SM. Pulse pressure, prehypertension, and mortality: the San Antonio heart study. Am J Hypertens. 2009;22(11):1219–26.PubMedCrossRefGoogle Scholar
  39. 39.
    Hozawa A, Kuriyama S, Kakizaki M, Ohmori-Matsuda K, Ohkubo T, Tsuji I. Attributable risk fraction of prehypertension on cardiovascular disease mortality in the Japanese population: the Ohsaki Study. Am J Hypertens. 2009;22(3):267–72.PubMedCrossRefGoogle Scholar
  40. 40.
    Pednekar MS, Gupta R, Gupta PC. Association of blood pressure and cardiovascular mortality in India: Mumbai cohort study. Am J Hypertens. 2009;22(10):1076–84.PubMedCrossRefGoogle Scholar
  41. 41.
    Dorjgochoo T, Shu XO, Zhang X, et al. Relation of blood pressure components and categories and all-cause, stroke and coronary heart disease mortality in urban Chinese women: a population-based prospective study. J Hypertens. 2009;27(3):468–75.PubMedCrossRefGoogle Scholar
  42. 42.
    Tanaka F, Makita S, Onoda T, et al. Prehypertension subtype with elevated C-reactive protein: risk of ischemic stroke in a general Japanese population. Am J Hypertens. 2010;23(10):1108–13.PubMedCrossRefGoogle Scholar
  43. 43.
    Ishikawa Y, Ishikawa J, Ishikawa S, et al. Prehypertension and the risk for cardiovascular disease in the Japanese general population: the Jichi Medical School Cohort Study. J Hypertens. 2010;28(8):1630–7.PubMedCrossRefGoogle Scholar
  44. 44.
    Kim NH, Cho HJ, et al. Combined effect of high-normal blood pressure and low HDL cholesterol on mortality in an elderly Korean population: the South-West Seoul (SWS) study. Am J Hypertens. 2011;24(8):918–23.PubMedCrossRefGoogle Scholar
  45. 45.
    Hadaegh F, Mohebi R, Khalili D, Hasheminia M, Sheikholeslami F, Azizi F. High normal blood pressure is an independent risk factor for cardiovascular disease among middle-aged but not in elderly populations: 9-year results of a population-based study. J Hum Hypertens. 2013;27(1):18–23.PubMedCrossRefGoogle Scholar
  46. 46.
    Fukuhara M, Arima H, Ninomiya T, et al. Impact of lower range of prehypertension on cardiovascular events in a general population: the Hisayama Study. J Hypertens. 2012;30(5):893–900.PubMedCrossRefGoogle Scholar
  47. 47.
    Erbel R, Lehmann N, Möhlenkamp S, et al. Subclinical coronary atherosclerosis predicts cardiovascular risk in different stages of hypertension: result of the Heinz Nixdorf Recall Study. Hypertension. 2012;59(1):44–53.PubMedCrossRefGoogle Scholar
  48. 48.
    Wang Y, Wang QJ. The prevalence of prehypertension and hypertension among US adults according to the new joint national committee guidelines: new challenges of the old problem. Arch Intern Med. 2004;164:2126–34.PubMedCrossRefGoogle Scholar
  49. 49.
    Lloyd-Jones D, Adams R, Carnethon M, et al. Heart disease and stroke statistics—2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2009;119(3):e21–e181.PubMedCrossRefGoogle Scholar
  50. 50.
    Huang Y, Wang S, Cai X, Mai W, Hu Y, Tang H, et al. Prehypertension and incidence of cardiovascular disease: a meta-analysis. BMC Med. 2013;11:177. doi: 10.1186/1741-7015-11-177.PubMedCrossRefGoogle Scholar
  51. 51.
    Bowman TS, Sesso HD, Glynn RJ, Gaziano JM. JNC 7 category and risk of cardiovascular death in men: are there differences by age? Am J Geriatr Cardiol. 2005;14(3):126–31.PubMedCrossRefGoogle Scholar
  52. 52.
    Arima H, Murakami Y, Lam TH, et al. Effects of prehypertension and hypertension subtype on cardiovascular disease in the Asia-Pacific Region. Hypertension. 2012;59(6):1118–23.PubMedCrossRefGoogle Scholar
  53. 53.
    Writing Group Members, Lloyd-Jones D, Adams RJ, et al. Heart disease and stroke statistics: 2010 update: a report from the American Heart Association. Circulation. 2010;121:e46–e215.PubMedCrossRefGoogle Scholar
  54. 54.
    Lee M, Saver JL, Chang B, Chang KH, Hao Q, Ovbiagele B. Presence of baseline prehypertension and risk of incident stroke: a meta-analysis. Neurology. 2011;77(14):1330–7.PubMedCrossRefGoogle Scholar
  55. 55.
    Sipahi I, Swaminathan A, Natesan V, Debanne SM, Simon DI, Fang JC. Effect of antihypertensive therapy on incident stroke in cohorts with prehypertensive blood pressure levels: a meta-analysis of randomized controlled trials. Stroke. 2012;43(2):432–40.PubMedCrossRefGoogle Scholar
  56. 56.
    Butler J, Kalogeropoulos AP, Georgiopoulou VV, et al. Systolic blood pressure and incident heart failure in the elderly. The cardiovascular health study and the health, ageing and body composition study. Heart. 2011;97(16):1304–11.PubMedCrossRefGoogle Scholar
  57. 57.
    The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1997; 157:2413–46.Google Scholar
  58. 58.
    1999 World Health Organization-International Society of Hypertension guidelines for the management of hypertension, Guidelines Subcommittee. J Hypertens. 1999; 17:151–83.Google Scholar
  59. 59.
    Mancia G, De Backer G, Dominiczak A, et al. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007;25(6):1105–87.PubMedCrossRefGoogle Scholar
  60. 60.
    European Society of Hypertension-European Society of Cardiology Guidelines Committee. 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens. 2003;21:1011–53.CrossRefGoogle Scholar
  61. 61.
    Ogihara T, Kikuchi K, Matsuoka H, et al. The Japanese society of hypertension guidelines for the management of hypertension (JSH 2009). Hypertens Res. 2009;32:3–107.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Xiaofan Guo
    • 1
  • Xiaoyu Zhang
    • 2
  • Liang Guo
    • 1
  • Zhao Li
    • 1
  • Liqiang Zheng
    • 3
  • Shasha Yu
    • 1
  • Hongmei Yang
    • 1
  • Xinghu Zhou
    • 1
  • Xingang Zhang
    • 1
  • Zhaoqing Sun
    • 4
  • Jue Li
    • 5
  • Yingxian Sun
    • 1
    Email author
  1. 1.Department of CardiologyThe First Hospital of China Medical UniversityShenyangPeople’s Republic of China
  2. 2.Shenyang Eye Research InstituteThe Fourth People’ HospitalShenyangPeople’s Republic of China
  3. 3.Department of Clinical Epidemiology, LibraryShengjing Hospital of China Medical UniversityShenyangPeople’s Republic of China
  4. 4.Department of CardiologyShengjing Hospital of China Medical UniversityShenyangPeople’s Republic of China
  5. 5.Heart, Lung and Blood Vessel CenterTongji UniversityShanghaiPeople’s Republic of China

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